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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A culture of mouse cells containing a 1,000-nucleotide deletion mutant of Moloney murine leukemia virus has been isolated. The deletion did not affect the size or function of the 21S mRNA that encodes the env gene products. Both the deleted RNA and the 21S mRNA were recovered in polyribosomes. Cells containing the deleted virus made no detectable Pr180gag-pol. Pr65gag synthesis with also absent, but a 45,000-molecular-weight gag gene product was found that might be encoded by the deleted genome. Biosynthesis of Pr80env proceeded normally in these cells; the intracellular precursor was cleaved and migrated to the cell surface as gp70. The cells could not be superinfected by homologous Moloney murine leukemia virus presumably because of surface restriction due to the gp70. Although the cells express the Moloney murine leukemia virus gp70 on their surface, they will not make pseudotypes after infection with vesicular stomatitis virus implying that Pr65gag may play a critical role in pseudotype formation. Induction of endogenous virus expression in the cells carrying the deletion mutant generated an N-tropic murine leukemia virus that can fuse XC cells. This may represent a recombinant between the deletion mutant and an endogenous virus.
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PMID:Isolation and characterization of a mouse cell line containing a defective Moloney murine leukemia virus genome. 22 65

Feline leukemia viruses (FeLVs) belonging to the C subgroup induce aplastic anemia in domestic cats and have the ability, unique among FeLV strains, to proliferate in guinea pig fibroblasts in tissue culture. Previous studies have shown that the pathogenic and host range specificity of a prototype molecular clone of FeLV-C [FeLV-Sarma-C (FSC)] colocalize to a region encoding the 3' 73 amino acids of the pol gene product and the N-terminal 241 amino acids of the envelope surface glycoprotein named SU. Here, we amplified, via PCR, cloned, and sequenced the SU coding sequence from three additional anemia-inducing subgroup C FeLV isolates. Chimeric viruses were constructed by replacement of fragments of FeLV-C envelope genes into the FeLV-A prototype virus 61E. Using a modified vesicular stomatitis virus-FeLV pseudotype assay, we demonstrated that the subgroup C receptor specificity for each virus was determined by changes within the N-terminal 87-92 amino acids of SU, in which most changes occurred within the 15- to 20-amino-acid first variable region (V1). Determinants for growth in guinea pig cells colocalized to this region. Despite the consistent localization of biological determinants, the only consistent features that distinguished the deduced FeLV-A and FeLV-C proteins was one lysine-to-arginine change and a structural prediction of an alpha-helix in FeLV-A proteins versus random coil in FeLV-C proteins within V1. However, arginine in equilibrium with lysine substitutions were not sufficient to convert the subgroup A virus to the subgroup C phenotype or vice versa. Thus, certain distinct structural changes within the N-terminal region of FeLV SU can result in convergent viral phenotypes.
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PMID:Feline leukemia virus subgroup C phenotype evolves through distinct alterations near the N terminus of the envelope surface glycoprotein. 132 57

Feline immunodeficiency virus (FIV) has morphological, physical and biochemical characteristics similar to human immunodeficiency virus (HIV), the cause of AIDS in man. However, it is antigenically and genetically distinct from HIV; an antigenic relatedness with equine infectious anaemia virus has been demonstrated. FIV has been molecularly cloned and sequenced. Diagnostic tests are commercially available and attempts at preparing inactivated, subunit and molecularly engineered vaccines are being made in different laboratories. During FIV infection a transient primary illness can be recognized, with fever, neutropenia and lymphadenopathy. After a long period of clinical normalcy a secondary stage is distinguished with signs of an immunodeficiency-like syndrome. The incubation period for this stage can be as long as 5 years, during which gradual impairment of immune function develops. Many FIV-infected cats are presented for the first time showing vague signs of illness: recurrent fevers, emaciation, lack of appetite, lymphadenopathy, anaemia, leucopenia and behavioural changes. Later, the predominant clinical signs observed are chronic stomatitis/gingivitis, enteritis, upper respiratory tract infections, and infections of the skin. Neoplasias, neurological, immunological and haematological disorder are seen in a smaller proportion. The immunodeficiency-like syndrome is progressive over a period of months to years. Concomitant infection with feline leukaemia virus has been shown to accelerate the progression of disease. In vitro, phenotypic mixing between FIV and an endogenous feline oncovirus (RD114) has been demonstrated which leads to a broadening of the cell spectrum of the lentivirus. Bovine immunodeficiency virus (BIV) has been isolated only once, and all attempts to obtain additional isolates have failed; it has been recovered from the leucocytes of cattle with persistent lymphocytosis, lymphadenopathy, lesions in the central nervous system, progressive weakness and emaciation. As with the feline representative, BIV also was found to possess a lentivirus morphology and to encode a reverse transcriptase with Mg++ preference; it replicates and induces syncytia in a variety of embryonic bovine tissues in vitro. Antigenic analyses have demonstrated a conservation of epitopes between the major core protein of BIV and HIV. The original isolate has been molecularly cloned and sequenced. Besides the three large open reading frames (ORFs) comprising the gag, pol, and env genes common to all replication-competent retroviruses, five additional small ORFs were found. Numerous point mutations and deletions were found, mostly in the env-encoding ORF. These data suggest that, within a single virus isolate, BIV displays extensive genomic variation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Animal immunodeficiency viruses. 133 43

A single interferon (IFN) induction-suppressing particle (ISP) of vesicular stomatitis virus (VSV) blocked completely the yield of IFN in a cell otherwise programmed to produce IFN. With mouse L cells as hosts, one lethal hit of UV radiation (D37 = 52.5 ergs/mm2) to the VSV genome sufficed to inactivate ISP activity; however, with "aged" primary chick embryo cells as hosts, it took 198 lethal hits (D37 = 10,395 ergs/mm2). ISP expression in chick cells did not require virus replication or amplified RNA synthesis, but did involve functional virion-associated L protein. ISP in chick cells also were capable of inhibiting, in a multiplicity-dependent manner, the plaquing efficiency of two viruses that require cellular polymerase II (pol II) for replication, e.g., pseudorabies and influenza. The refractory state to IFN inducibility that resulted from infection of chick cells with ISP (VSV tsO5 [UV = 100 hits]) was still extant after 6 days. In contrast, the plaquing efficiency of pseudorabies virus returned to control levels by 5 h after ISP infection. Chick cells infected with UV ISP remained viable, served as hosts for the replication of other viruses, and could be subcultured. Models are presented to account for these contrasting effects. The involvement of viral plus-strand leader RNA as an inhibitor of cellular pol II-dependent RNA synthesis, and the multifunctional activities of the virion-associated L protein, are discussed as possible molecules involved in the action of ISP in chick cells.
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PMID:Interferon induction by viruses. XV. Biological characteristics of interferon induction-suppressing particles of vesicular stomatitis virus. 244 Sep 58

We recently reported that vesicular stomatitis virus pol R mutants contain a template-associated N-protein alteration which allows for efficient readthrough of leader RNA termination sites in vitro (Perrault et al., Cell 35:175-185, 1983). We show here that in vitro RNA synthesis mediated by pol R virions is much more resistant to replacement of ATP by the analog beta,gamma-imido ATP than by wild-type virus (approximately 50% inhibition versus approximately 95%). Characterization of beta,gamma-imido ATP-resistant and control products by size, polyadenylic acid content, frequency of initiation at the 3' end of the template, and readthrough of the leader-N gene junction leads us to conclude the following: (i) most likely, the ATP dependence of the transcription process primarily reflects a requirement for initiation or entry of the polymerase at the 3' end of the template; (ii) this requirement is largely bypassed in the mutant pol R viruses; (iii) the synthesis of small, internally initiated transcripts by wild-type virus is less dependent on ATP than that of leader RNA; and (iv) termination at leader RNA sites is not directly affected when beta,gamma-imido ATP is added before initiation of synthesis. These results are discussed in terms of the possible roles of ATP and the nucleocapsid protein in initiation and termination of vesicular stomatitis virus RNA synthesis.
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PMID:ATP dependence of vesicular stomatitis virus transcription initiation and modulation by mutation in the nucleocapsid protein. 608 89

Small leader RNAs, copied from the extreme 3' ends of the minus and plus strands of the vesicular stomatitis virus (VSV) genome, are thought to play a central role in the regulation of viral transcription and replication. We describe here a novel class of VSV mutants, denoted pol R, in which termination at leader sites in vitro is specifically suppressed. We have assayed for the presence of leader RNAs and readthrough transcripts in reaction products from standard virion templates (plus leader) and defective interfering particle templates (minus leader). In both cases, mutant virions gave rise to a much higher proportion of readthrough transcripts than wild type (greater than 80% vs approximately 10%). Reconstitution experiments with separated ribonucleoprotein (RNP) templates and polymerase protein fractions revealed, surprisingly, that the N protein moiety of the RNP template was responsible for readthrough. This conclusion was further supported by protein analyses that showed a similar charge change in the N protein of two independently isolated pol R VSV mutants. These results lead us to propose that modification of the N protein may regulate termination at leader RNA sites.
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PMID:RNP template of vesicular stomatitis virus regulates transcription and replication functions. 631 23

We have generated a human 293-derived retroviral packaging cell line (293GPG) capable of producing high titers of recombinant Moloney murine leukemia virus particles that have incorporated the vesicular stomatitis virus G (VSV-G) protein. To achieve expression of the retroviral gag-pol polyprotein, the precise coding sequences for gag-pol were introduced into a vector which utilizes totally nonretroviral signals for gene expression. Because constitutive expression of the VSV-G protein is toxic in 293 cells, we used the tetR/VP 16 transactivator and teto minimal promoter system for inducible, tetracycline-regulatable expression of VSV-G. After stable transfection of the 293GPG packaging cell line with the MFG.SnlsLacZ retroviral vector construct, it was possible to readily isolate stable virus-producing cell lines with titers approaching 10(7) colony-forming units/ml. Transient transfection of 293GPG cells using a modified version of MFG.SnlsLacZ, in which the cytomegalovirus IE promoter was used to drive transcription of the proviral genome, led to titers of approximately 10(6) colony-forming units/ml. The retroviral/VSV-G pseudotypes generated using 293GPG cells were significantly more resistant to human complement than commonly used amphotropic vectors and could be highly concentrated (> 1000-fold). This new packaging cell line may prove to be particularly useful for assessing the potential use of retroviral vectors for direct in vivo gene transfer. The design of the cell line also provides at least theoretical advantages over existing cell lines with regard to the possible release of replication-competent virus.
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PMID:A stable human-derived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus G pseudotypes. 887 47

It has been technically difficult to generate recombinant adenoviruses encoding genes for cytotoxic products such as vesicular stomatitis virus G-protein (VSV-G), which is too toxic for the host cells to allow adenoviral propagation. In our companion paper (Yoshida, Y., and Hamada, H., Biochem. Biophys. Res. Commun., 230, 426-430, 1997), a tetracycline-inducible adenovirus system is reported. The inducible expression system enabled us to generate recombinant adenoviruses encoding genes for the cytotoxic viral VSV-G product. In this study, we generated recombinant adenoviruses encoding VSV-G and MoMLV gag-pol genes, both under the tetracycline-controllable promoter, and attempted retroviral packaging. Simultaneous infection of these adenoviruses together with tetracycline-transactivator (NtTA) expression resulted in efficient VSVG-pseudotyped retroviral packaging. Adenovirus-mediated recombinant retrovirus generation will be useful in studies with various pseudotyped mutants, as well as in assays for retrovirus-related genes and their products.
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PMID:VSV-G-pseudotyped retroviral packaging through adenovirus-mediated inducible gene expression. 912 85

We report here on stable prepackaging cell lines which can be converted into packaging cell lines for high-titer vesicular stomatitis virus G protein (VSV-G)-pseudotyped retrovirus vectors by the introduction of Cre recombinase-expressing adenovirus. The generated prepackaging cell lines constitutively express the gag-pol genes and contain an inducible transcriptional unit for the VSV-G gene. From this unit, the introduced Cre recombinase excised both a neomycin resistance (Neo(r)) gene and a poly(A) signal flanked by a tandem pair of loxP sequences and induced transcription of the VSV-G gene from the same promoter as had been used for Neo(r) expression. By inserting an mRNA-destabilizing signal into the 3' untranslated region of the Neo(r) gene to reduce the amount of Neo(r) transcript, we were able efficiently to select the clones capable of inducing VSV-G at high levels. Without the introduction of Cre recombinase, these cell lines produce neither VSV-G nor any detectable infectious virus at all, even after the transduction of a murine leukemia virus-based retrovirus vector encoding beta-galactosidase. They reproducibly produced high-titer virus stocks of VSV-G-pseudotyped retrovirus (1.0 x 10(6) infectious units/ml) from 3 days after the introduction of Cre recombinase. We also present evidence that VSV-G-producing cells are still fully susceptible to transduction by VSV-G pseudotypes. However, in this vector-producing system, which regulates VSV-G pseudotype production in an all-or-none manner, the integration of vector DNA into packaging cell lines would be minimized. We further show that heparin significantly inhibits retransduction of VSV-G pseudotypes in the culture fluids of packaging cell lines, leading to a two- to fourfold increase in the yield of the pseudotypes after induction. This vector-producing system was very stable and should be advantageous in human gene therapy.
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PMID:A new system for stringent, high-titer vesicular stomatitis virus G protein-pseudotyped retrovirus vector induction by introduction of Cre recombinase into stable prepackaging cell lines. 944 7

In the absence of envelope gene expression, retrovirus packaging cell lines expressing Moloney murine leukemia virus (MLV) gag and pol genes produce large amounts of noninfectious virus-like particles that contain reverse transcriptase, processed Gag protein, and viral RNA (gag-pol RNA particles). We demonstrate that these particles can be made infectious in an in vitro, cell-free system by the addition of a surrogate envelope protein, the G spike glycoprotein of vesicular stomatitis virus (VSV-G). The appearance of infectivity is accompanied by physical association of the G protein with the immature, noninfectious virus particles. Similarly, exposure in vitro of wild-type VSV-G to a fusion-defective pseudotyped virus containing a mutant VSV-G markedly increases the infectivity of the virus to titers similar to those of conventional VSV-G pseudotyped viruses. Furthermore, similar treatment of an amphotropic murine leukemia virus significantly allows infection of BHK cells not otherwise susceptible to infection with native amphotropic virus. The partially cell-free virus maturation system reported here should be useful for studies aimed at the preparation of tissue-targeted retrovirus vectors and will also aid in studies of nucleocapsid-envelope interactions during budding and of virus assembly and virus-receptor interactions during virus uptake into infected cells. It may also represent a potentially useful step toward the eventual development of a completely cell-free retrovirus assembly system.
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PMID:In vitro cell-free conversion of noninfectious Moloney retrovirus particles to an infectious form by the addition of the vesicular stomatitis virus surrogate envelope G protein. 965 75


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